Tsuyoshi Kobayashi 1, Masayuki Kaneko 2, Mamoru Narukawa 2
Background: The incidence of vertebral fracture is commonly used as a primary endpoint in randomized clinical trials of pharmaceutical agents for osteoporosis. In order to investigate the impact of ethnic/regional difference in osteoporosis clinical trials on the incidence of vertebral fracture, we examined the correlation between the incidence of vertebral fracture in the placebo group and baseline bone mineral density (BMD), ethnic and regional differences, or other factors by meta-regression analysis.
Methods: We studied a total of 21 trials involving 28,425 patients treated with placebo, which were identified through MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials.
Results: A univariate meta-regression showed a significant correlation between the proportion of subjects experiencing new vertebral fracture and the proportion of Caucasian subjects (coefficient = 0.223, [Formula: see text]), and the proportion of subjects with prevalent vertebral fracture (0.161, [Formula: see text]). Baseline lumbar spine BMD did not show significant correlations. As a result of multivariate meta-regression analysis with the factors with [Formula: see text] by the univariate meta-regression, the proportion of subjects with prevalent vertebral fracture was identified as an influencing factor (0.139, [Formula: see text]).
Conclusions: The multivariate meta-regression showed that prevalent vertebral fracture was the most important factor to predict subsequent vertebral fracture. In addition, considering the results of the univariate meta-regression analysis, we suggest that the ethnic/regional difference should be considered as one of the important factors that influence the incidence of new vertebral fracture, a primary endpoint of osteoporosis study, when the Caucasian reference range is used in clinical trials.